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Renal Artery Dopplers in Twin Twin Transfusion Syndrome

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ClinicalTrials.gov Identifier: NCT03449823
Recruitment Status : Completed
First Posted : February 28, 2018
Last Update Posted : July 18, 2018
Sponsor:
Information provided by (Responsible Party):
Russell Miller, Columbia University

Brief Summary:

Twin-twin transfusion syndrome (TTTS) is a complication affecting 10-15% of monochorionic, diamniotic (MCDA) twin pregnancies. Unevenly distributed blood flow across a shared placental circulation results in a volume-restricted donor twin and a volume-overloaded recipient twin, and TTTS has high perinatal morbidity and mortality without treatment.

Differential donor and recipient findings in TTTS can be observed upon ultrasound evaluation. TTTS is classified according to the Quintero staging system, which evaluates amniotic fluid volumes, fetal bladders, Doppler study of the umbilical artery and ductus venosus, and for the presence of hydrops or death. However, due to seemingly complex and variable disease pathophysiology, the Quintero system cannot predict outcomes on a case-by-case basis.

Prior studies have associated fetal renal artery Doppler ultrasound measurements with amniotic fluid volume in singleton pregnancies. In fetuses with placental insufficiency, adaptive circulatory changes maintain adequate oxygen delivery to vital organs such as the heart, brain, and adrenals, with a consequent deprivation to splanchnic organs. In the fetal kidney, as vascular resistance increases during hypoxia, renal perfusion decreases proportionately. These changes are reflected in renal artery Doppler findings. As these same adaptations are believed to occur in donor twins, renal artery Doppler studies may also be of value in the TTTS evaluation.

This study plans to perform renal artery Doppler assessments in MCDA twins complicated by TTTS, and compare them to measurements in gestational-age equivalent MCDA twins without TTTS. If findings differ significantly, it would support further investigation into the use of renal artery Doppler studies for the evaluation of complicated MCDA twins.


Condition or disease Intervention/treatment
Twin Twin Transfusion Syndrome Diagnostic Test: Doppler ultrasound of fetal renal artery

Detailed Description:

TTTS, which complicates 10-15% of MCDA twin pregnancies, is characterized by a net imbalance of volume between twins, mediated through abnormal placental blood vessel anastomoses that connect the two placental circulations. Clinically, the "donor" twin develops features of anemia and hypovolemia, while the "recipient" twin shows signs of hypervolemia and hypertensive fluid overload. If untreated, the syndrome has a perinatal mortality rate as high as 80-100%. Although modern intrauterine therapies have improved the rates of fetal death, significant risks of morbidity and mortality remain even after treatment.

Twin-twin transfusion syndrome is most commonly classified according to a staging system developed by Quintero et al in 1999, which is based on discrete, categorical ultrasound findings (amniotic fluid volume, presence/absence of a fetal bladder, umbilical artery Doppler studies, fetal hydrops, and death). The system includes 5 stages ranging from mild disease with isolated discordant amniotic fluid volumes, to severe disease with demise of one or both twins. Although this system has some prognostic value, it also has significant limitations due to the highly complex physiologic conditions that are involved in the disease. For example, some criteria in the staging system are not consistently representative of fetal physiology. Additionally, the stages do not correlate well with overall perinatal survival or with outcomes following intrauterine therapies.

Recent work has demonstrated that the complex pathophysiology of twin-twin transfusion syndrome involves a discordant activation of the renin angiotensin system (RAS). RAS is normally important in fluid and salt regulation in both the adult and the fetus, and TTTS in marked hypovolemia and hypervolemia in monozygous fetuses within the same maternal environment. The renal RAS in the donor is up-regulated, presumably as a consequence of hypovolemia. The recipient is also exposed to high levels or RAS components, either due to the transfusion of these components from the donor via anastomoses, or via discordant placental RAS activation, resulting in a hypertensive, hypervolemic state.

Multiple studies have identified a correlation between Doppler assessment of the fetal renal artery and the development of oligohydramnios, a hypovolemic state, in singleton pregnancies. However, the use of renal artery Doppler studies has not yet been fully evaluated in twin gestations. In particular, it has not been evaluated in MCDA twin gestations complicated by TTTS, the pathophysiology of which involves significant alterations in fetal volume and fluid status.

This project is intended to serve as a single-center study to determine if there is indeed a difference in renal artery Doppler parameters in sets of MCDA twins with TTTS compared to sets of MCDA twins without TTTS. The identification of a significant difference would potentially provide support for further investigation into this measurement as a screening tool or prognostic indicator when applied to MCDA twin pregnancies.

Secondary goals of this study include: comparing donor to recipient renal artery Doppler findings among pregnancies with TTTS, evaluating serial renal artery Doppler findings over time per pregnancy, and evaluating pre- and post-therapy renal artery Doppler findings in those pregnancies undergoing therapy for TTTS.

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Study Type : Observational
Actual Enrollment : 24 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Are Renal Artery Doppler Indices Different Between Monochorionic Diamniotic Twins With Twin-twin Transfusion Syndrome and Monochorionic Diamniotic Twins Without Twin-twin Transfusion Syndrome?
Actual Study Start Date : September 9, 2016
Actual Primary Completion Date : March 21, 2018
Actual Study Completion Date : June 30, 2018


Group/Cohort Intervention/treatment
TTTS Cases
Cases of monochorionic / diamniotic twin pregnancies diagnosed with twin-twin transfusion syndrome.
Diagnostic Test: Doppler ultrasound of fetal renal artery
Doppler ultrasound assessment of the proximal fetal renal artery to with measurement of the peak systolic velocity, resistive index, pulsatility index, and systolic/diastolic ratio.

MCDA Controls
Controls of monochorionic / diamniotic twin pregnancies without a diagnosis of twin-twin transfusion syndrome.
Diagnostic Test: Doppler ultrasound of fetal renal artery
Doppler ultrasound assessment of the proximal fetal renal artery to with measurement of the peak systolic velocity, resistive index, pulsatility index, and systolic/diastolic ratio.




Primary Outcome Measures :
  1. Fetal renal artery Doppler PSV for twin A [ Time Frame: Obtained at the time of enrollment. ]
    Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the peak systolic velocity for twin A.

  2. Fetal renal artery Doppler RI for twin A [ Time Frame: Obtained at the time of enrollment. ]
    Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the resistive index for twin A.

  3. Fetal renal artery Doppler PI for twin A [ Time Frame: Obtained at the time of enrollment. ]
    Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the pulsatility index for twin A.

  4. Fetal renal artery Doppler PSV for twin B [ Time Frame: Obtained at the time of enrollment. ]
    Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the peak systolic velocity for twin B.

  5. Fetal renal artery Doppler RI for twin B [ Time Frame: Obtained at the time of enrollment. ]
    Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the resistive index for twin B.

  6. Fetal renal artery Doppler PI for twin B [ Time Frame: Obtained at the time of enrollment. ]
    Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the pulsatility index for twin B.


Secondary Outcome Measures :
  1. Post-laser fetal renal artery Doppler PSV for twin A [ Time Frame: Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided. ]
    Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the peak systolic velocity for twin A.

  2. Post-laser fetal renal artery Doppler RI for twin A [ Time Frame: Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided. ]
    Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the resistive index for twin A.

  3. Post-laser fetal renal artery Doppler PI for twin A [ Time Frame: Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided. ]
    Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the pulsatility index for twin A.

  4. Post-laser fetal renal artery Doppler PSV for twin B [ Time Frame: Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided. ]
    Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the peak systolic velocity for twin B.

  5. Post-laser fetal renal artery Doppler RI for twin B [ Time Frame: Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided. ]
    Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the resistive index for twin B.

  6. Post-laser fetal renal artery Doppler PI for twin B [ Time Frame: Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided. ]
    Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the pulsatility index for twin B.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Sampling Method:   Non-Probability Sample
Study Population
The subject population will consist of pregnant women with monochorionic / diamniotic (MCDA) twin pregnancies with and without twin-twin transfusion syndrome (TTTS). This population is selected in order to investigate twin-twin transfusion syndrome, which is a disease process that is unique to pregnancies with monochorionic / diamniotic twins. Patients will be included in the study if they have a diagnosis of a MCDA twin gestation beyond the first trimester or pregnancy (greater than 14 weeks gestation).
Criteria

Inclusion Criteria:

  • pregnant women with monochorionic / diamniotic (MCDA) twin pregnancies with and without twin-twin transfusion syndrome (TTTS)
  • greater than 14 weeks gestation

Exclusion Criteria:

  • higher-order multiple gestation
  • sonographic evidence of a major structural fetal anomaly (exceptions to this structural fetal anomaly exclusion are acquired recipient twin cardiac changes that are known to be associated with TTTS - these cases may be considered for study inclusion)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03449823


Locations
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United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Investigators
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Study Director: Joses Jain, MD Columbia University
Principal Investigator: Russell Miller, MD Columbia University
Publications:

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Responsible Party: Russell Miller, Assistant Professor of Obstetrics and Gynecology, Columbia University
ClinicalTrials.gov Identifier: NCT03449823    
Other Study ID Numbers: AAAQ9660
First Posted: February 28, 2018    Key Record Dates
Last Update Posted: July 18, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share individual participant data with other researchers.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Russell Miller, Columbia University:
Renal Artery Doppler
Additional relevant MeSH terms:
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Fetofetal Transfusion
Syndrome
Disease
Pathologic Processes
Anemia, Neonatal
Anemia
Hematologic Diseases
Infant, Newborn, Diseases